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3uou

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Revision as of 17:04, 22 March 2017

Crystal structure of the Kunitz-type protease inhibitor ShPI-1 Lys13Leu mutant in complex with pancreatic elastase

Structural highlights

3uou is a 2 chain structure with sequence from Carribean sea anemone and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Pancreatic elastase, with EC number 3.4.21.36
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CELA1_PIG] Acts upon elastin. [ISH1_STOHE] Active against serine, cysteine, and aspartic proteinases. Can bind vertebrate trypsin and chymotrypsin.^[1] ^[2]

Publication Abstract from PubMed

Elastase-like enzymes are involved in important diseases, such as acute pancreatitis, chronic inflammatory lung diseases, and cancer. Structural insights into the interaction with specific inhibitors will contribute to develop novel anti-elastase compounds that resist rapid oxidation and proteolysis. Proteinaceous Kunitz-type inhibitors homologous to the bovine pancreatic trypsin inhibitor (BPTI) provide a suitable scaffold, but structural aspects of their interaction with elastase-like enzymes have not been elucidated. Here, we increased the selectivity of ShPI-1, a versatile serine protease inhibitor from the sea anemone Stichodactyla helianthus with high biomedical and biotechnological potential, towards elastase-like enzymes by substitution of the P1 residue (Lys13) with leucine. The variant (rShPI-1/K13L) exhibits a novel anti-porcine pancreatic elastase (PPE) activity, together with a significantly improved inhibition of human neuthrophil elastase (HNE) and chymotrypsin. The crystal structure of the PPE-rShPI-1/K13L complex determined at 2.0 A resolution provided first details of the canonical interaction between a BPTI-Kunitz-type domain and elastase-like enzymes. In addition to the essential impact of the variant P1 residue for complex stability, the interface is improved by increased contributions of the primary and secondary binding loop as compared to similar trypsin and chymotrypsin complexes. Comparison of the interaction network with elastase complexes of canonical inhibitors from the chelonianin family supports a key role of the P3 site in ShPI-1 in directing its selectivity against pancreatic and neutrophil elastases. Our results provide the structural basis for site-specific mutagenesis to further improve the binding affinity and/or to direct the selectivity of BPTI-Kunitz-type inhibitors towards elastase-like enzymes.

Three-dimensional structure of a Kunitz-type inhibitor in complex with an elastase-like enzyme.,Garcia-Fernandez R, Perbandt M, Rehders D, Ziegelmueller P, Piganeau N, Hahn U, Betzel C, de Los Angeles Chavez M, Redecke L J Biol Chem. 2015 Apr 15. pii: jbc.M115.647586. PMID:25878249^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Delfin J, Martinez I, Antuch W, Morera V, Gonzalez Y, Rodriguez R, Marquez M, Saroyan A, Larionova N, Diaz J, Padron G, Chavez M. Purification, characterization and immobilization of proteinase inhibitors from Stichodactyla helianthus. Toxicon. 1996 Nov-Dec;34(11-12):1367-76. PMID:9027993
↑ Garcia-Fernandez R, Pons T, Perbandt M, Valiente PA, Talavera A, Gonzalez-Gonzalez Y, Rehders D, Chavez MA, Betzel C, Redecke L. Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor. J Struct Biol. 2012 Sep 5. pii: S1047-8477(12)00240-7. doi:, 10.1016/j.jsb.2012.08.009. PMID:22975140 doi:http://dx.doi.org/10.1016/j.jsb.2012.08.009
↑ Garcia-Fernandez R, Perbandt M, Rehders D, Ziegelmueller P, Piganeau N, Hahn U, Betzel C, de Los Angeles Chavez M, Redecke L. Three-dimensional structure of a Kunitz-type inhibitor in complex with an elastase-like enzyme. J Biol Chem. 2015 Apr 15. pii: jbc.M115.647586. PMID:25878249 doi:http://dx.doi.org/10.1074/jbc.M115.647586

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uou"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Kunitz-type protease inhibitor ShPI-1 Lys13Leu mutant in complex with pancreatic elastase==
 <StructureSection load='3uou' size='340' side='right' caption='[[3uou]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uou OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uou RCSB], [http://www.ebi.ac.uk/pdbsum/3uou PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uou OCA], [http://pdbe.org/3uou PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uou RCSB], [http://www.ebi.ac.uk/pdbsum/3uou PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uou ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3uou" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3uou

From Proteopedia

Revision as of 17:04, 22 March 2017

Crystal structure of the Kunitz-type protease inhibitor ShPI-1 Lys13Leu mutant in complex with pancreatic elastase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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